Origin of congenital coronary arterio-ventricular fistulae from anomalous epicardial and myocardial development.
Exp Mol Med
; 55(1): 228-239, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36653444
ABSTRACT
Coronary Artery Fistulae (CAFs) are cardiac congenital anomalies consisting of an abnormal communication of a coronary artery with either a cardiac chamber or another cardiac vessel. In humans, these congenital anomalies can lead to complications such as myocardial hypertrophy, endocarditis, heart dilatation, and failure. Unfortunately, despite their clinical relevance, the aetiology of CAFs remains unknown. In this work, we have used two different species (mouse and avian embryos) to experimentally model CAFs morphogenesis. Both conditional Itga4 (alpha 4 integrin) epicardial deletion in mice and cryocauterisation of chick embryonic hearts disrupted epicardial development and ventricular wall growth, two essential events in coronary embryogenesis. Our results suggest that myocardial discontinuities in the embryonic ventricular wall promote the early contact of the endocardium with epicardial-derived coronary progenitors at the cardiac surface, leading to ventricular endocardial extrusion, precocious differentiation of coronary smooth muscle cells, and the formation of pouch-like aberrant coronary-like structures in direct connection with the ventricular lumen. The structure of these CAF-like anomalies was compared with histopathological data from a human CAF. Our results provide relevant information for the early diagnosis of these congenital anomalies and the molecular mechanisms that regulate their embryogenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Coração
/
Cardiopatias Congênitas
Tipo de estudo:
Screening_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article